Synthetic method for diazepamum drug intermediate 2-amino-5-chloro-benzophenone
A technology for benzadiazole and a synthesis method, which is applied in chemical instruments and methods, preparation of organic compounds, organic chemistry, etc., can solve problems such as long reaction time, and achieve the effects of shortening reaction time and improving reaction yield.
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Embodiment 1
[0022] A kind of synthetic method of benzodiazepine medicine intermediate 2-amino-5-chloro-benzophenone, comprises the steps:
[0023] A. In a reaction vessel equipped with a stirrer and a reflux condenser, add 0.26mol of 5-chloro-3-phenyl-benzisoxazole, with a mass fraction of 30% 2-bromo-5-fluoronitrobenzene Solution 390ml, nickel chloride powder 0.46mol, control the stirring speed at 190rpm, raise the solution temperature to 78°C, and reflux for 120min;
[0024] B. Add 90ml of 4-chlorophenethylamine solution with a mass fraction of 21%, slowly add a ethylene glycol dimethyl ether solution with a mass fraction of 37%, control the addition time at 110min, and continue the reflux reaction for 5h;
[0025] C. Add 200ml of sodium bicarbonate solution with a mass fraction of 27%, lower the solution temperature to 16°C, decolorize with molecular sieves, filter, concentrate the filtrate, lower the solution temperature to 5°C again, wash with a 70% triethylamine solution, and oxidiz...
Embodiment 2
[0027] A kind of synthetic method of benzodiazepine medicine intermediate 2-amino-5-chloro-benzophenone, comprises the steps:
[0028] A. In a reaction vessel equipped with a stirrer and a reflux condenser, add 0.26mol of 5-chloro-3-phenyl-benzisoxazole, and the mass fraction is 25% of 2-bromo-5-fluoronitrobenzene Solution 300ml, nickel chloride powder 0.46mol, control the stirring speed at 160rpm, increase the solution temperature to 70°C, and reflux for 90min;
[0029] B. Add 90ml of 4-chlorophenethylamine solution with a mass fraction of 15%, slowly add a ethylene glycol dimethyl ether solution with a mass fraction of 30%, control the addition time at 80min, and continue the reflux reaction for 3h;
[0030] C, adding 200ml of sodium bicarbonate solution with a mass fraction of 21%, lowering the solution temperature to 10°C, decolorizing with molecular sieves, filtering, and concentrating the filtrate, lowering the solution temperature to 2°C again, washing with a 60% trieth...
Embodiment 3
[0032] A kind of synthetic method of benzodiazepine medicine intermediate 2-amino-5-chloro-benzophenone, comprises the steps:
[0033] A. In a reaction vessel equipped with a stirrer and a reflux condenser, add 0.26mol of 5-chloro-3-phenyl-benzisoxazole, and the mass fraction is 29% of 2-bromo-5-fluoronitrobenzene Solution 360ml, nickel chloride powder 0.46mol, control the stirring speed at 170rpm, increase the solution temperature to 73°C, and reflux for 110min;
[0034] B. Add 90ml of 4-chlorophenethylamine solution with a mass fraction of 19%, slowly add a ethylene glycol dimethyl ether solution with a mass fraction of 36%, control the addition time at 90min, and continue the reflux reaction for 4h;
[0035] C, add mass fraction and be 28% sodium bicarbonate solution 200ml, reduce solution temperature to 13 ℃, decolorize with molecular sieve, filter, filtrate concentrates, reduce solution temperature to 3 ℃ again, mass fraction is 65% triethylamine solution washing, no Deh...
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